PB2177: MULTICENTRE RETROSPECTIVE OBSERVATIONAL STUDY ON PATIENTS WITH MYELOFIBROSIS IN PIEDMONT. ROLE OF INFLAMMATION AND DYSIMMUNITY. MFACTORS STUDY.
Authors: Valentina Bonuomo, Marco Armenio, Daniela Cilloni, Federico Itri, Monia Marchetti, Selene Grano, Carmen Fava
Journal: HemaSphere (2023)

Topic: 15. Myeloproliferative neoplasms - Biology & Translational Research Background: Primary Myelofibrosis is a clonal myeloproliferative neoplasm (MPNs) characterized by megakaryocytic and granulocytic hyperplasia that goes along with process of bone marrow fibrosis. Nowadays it’s well recognised the clonal origin of the disease. Megakaryocytes have a central pathogenetic role: their proliferation is responsible of an excessive release of fibrogenic cytokines followed by an extensive obliteration of the hematopoietic niche. Inflammatory pathway JAK/STAT is commonly known as the central pathogenetic mechanism of the disease but isn’t the sole pathway altered in PMF: there is evidence of some cytokines which are not suppressed by ruxolitinib and may respond to the inhibition of other inflammatory pathways like NfkB and MAPk. That could be the case of IL6- IL-8, IL-10 and TNF which are usually resistant to ruxolitinib and could therefore be potential target for new therapies. Besides it’s well known that flogosis and vascular damage can contribute to the increased rate of thrombotic and haemorrhagic events while cytokines storm has a clear correlation on the development of constitutional symptoms. Aims: The primary objective of this project is to identify possible prognostic factors of disease progression and to evaluate the occurrence of thromboembolic and infectious events, including markers of inflammation, metabolic alterations and autoimmunity as variables in the analysis. Methods: We conducted a cross-sectional study of myelofibrosis’ patients belonging to the centres of Turin - Mauriziano Hospital, Orbassano - San Luigi Hospital and Asti Hospital. Data were collected on 98 patients diagnosed from 19/7/2005 to 29/11/2021 using REDCap, a secure web application for building and managing databases on Electronic Case Report Forms (eCRFs). Therapies were stratified by DIPSS at baseline and at follow-up. To test the difference between the classes we have employed the Kruskal test for continuous variables and the Chi-Square test for categorical variables. Results: Among current therapies for myelofibrosis, a majority of patients on ruxolitinib treatment was observed (40 patients – 40%). 14 patients (14%) presented with infections in the post-diagnosis period, while cardiovascular complications were recorded both in the pre-diagnosis phase, predominantly of an arterial nature (8 patients - 8.7%), and in the post-diagnosis period, with a majority of events of a venous nature (8 patients – 8.7%). The presence of any concomitant autoimmune disease was investigated in a population of 13 patients. Overall, regardless of an immunological diagnosis, a single autoantibody positivity was observed in 54.9% of the patients and at least two or more positivities in 21% of the cases. Ferritin and IL6 values showed a direct correlation with the DIPSS score and a higher propensity for infectious complications. Summary/Conclusion: The results emphasise how increased values of ferritin and interleukin-6 correlate with more aggressive stages of the disease, we therefore highlight the potential importance of ferro-chelation to prevent clinical complications. Observing the prevalence of autoimmunity markers in the study population, we can hypothesise for myelofibrosis the presence of an additional autoimmune-based pathogenetic mechanism in other than the clonal one. More accurate data regarding progression disease could be obtained with the analysis of a larger population. Keywords: Myeloproliferative disorder, Myelofibrosis, Tumor immunity